An unconscious man was brought to an emergency room somewher

An unconscious man was brought to an emergency room somewhere in the western part of our fair state. It turned out that this man, who suffered from diabetes (type 1). had been vacationing on the Appalachian Trail for two days without taking his insulin. He had access to food and water. Below is a list of tissues and pathways. Your task is to: Estimate the relative flux through the indicated pathways in this patient. Are they faster or slower (or unchanged?) when the patient is in this nearly comatose state compared to when he gets normal amounts of insulin? Describe (briefly) one regulatory mechanism for each pathway and in each tissue that accounts for the predicted changes.

Solution

Answer

(a)

(1) Adipose:

The synthesis of fatty acid has become slower

(2) Muscle:

All the three processes (glycolysis, fatty acid synthesis, and glycogen synthesis) has become slower.

(3) Liver:

Here the Pentose phosphate pathway has unchanged, but glycolysis occurring at a faster rate; but there is a slowdown of gluconeogenesis, glycogen synthesis, and fatty acid synthesis.

(b)

(1) Adipose and (3) liver:

Acetyl-CoA carboxylase is the first enzyme of fatty acid synthesis, this will become inactive and fatty acid synthesis will become slower due to the lack of insulin. The cAMP-dependent phosphorylation of glycogen synthase causes its activation, thus the glycogen synthesis will be inhibited.

(2) Muscle:

Here the glucose uptake will be inhibited due to the inactive GLUT4, the glycolysis process will become slower.

(3) Liver:

The bifunctional Phosphofructokinase 2 (PFK2) or fructose bisphosphatase 2 (FBPase2) will be seen to be converting to the form with active FBPase-2, thus making glycolysis slower.

The decreasing fructose 2,6-bisphosphate will see allosterically stimulating the phosphofructokinase and will try to inhibit FBPase-1. This will result in the stimulation of gluconeogenesis.

(1) Adipose:	The synthesis of fatty acid has become slower
(2) Muscle:	All the three processes (glycolysis, fatty acid synthesis, and glycogen synthesis) has become slower.
(3) Liver:	Here the Pentose phosphate pathway has unchanged, but glycolysis occurring at a faster rate; but there is a slowdown of gluconeogenesis, glycogen synthesis, and fatty acid synthesis.